Electrical properties of bimolecular lipid membranes (BLM) are measured to study: (1) mechanisms of ion transport; (2) properties of transport systems isolated from natural cell membranes; (3) mechanisms of cytotoxicity; (4) the effect of the membrane potential on the disposition of membrane proteins. We have continued our studies with the hepatic asialoglycoprotein receptor (the hepatic binding protein, or HBP), which induces voltage-dependent increases in ion conductance across a BLM, and is probably translocated across the bilayer under the influence of the electric field in the presence of specific ligand or Ca++. These observations suggested a mechanism by which biological membranes might regulate the disposition of their proteins. We have carried out a theoretical analysis on the way electrostatic forces operating on charge clusters, found in transmembrane proteins, may determine the final orientation of the protein. To test the predictions of that analysis we are studying the topology with respect to the bilayer of mellitin, a peptide with a hydrophobic domain and a positively charged domain of amino acids. Under the influence of a trans-negative membrane potential mellitin induces an increase in BLM conductance, which is sensitive to pronase. We are also studying the interaction of clathrin with BLMs.